title: Hydrogen sulfide attenuates cardiac dysfunction after heart failure via induction of angiogenesis.
abstract: BACKGROUND
  Hydrogen sulfide (H2S) has been shown to induce angiogenesis in in vitro models and to promote vessel growth in the setting of hindlimb ischemia. The goal of the present study was to determine the therapeutic potential of a stable, long-acting H2S donor, diallyl trisulfide, in a model of pressure-overload heart failure and to assess the effects of chronic H2S therapy on myocardial vascular density and angiogenesis.
  
  
  RESULTS
  Transverse aortic constriction was performed in mice (C57BL/6J; 8-10 weeks of age). Mice received either vehicle or diallyl trisulfide (200 µg/kg) starting 24 hours after transverse aortic constriction and were followed up for 12 weeks using echocardiography. H2S therapy with diallyl trisulfide improved left ventricular remodeling and preserved left ventricular function in the setting of transverse aortic constriction. H2S therapy increased the expression of the proangiogenic factor, vascular endothelial cell growth factor, and decreased the angiogenesis inhibitor, angiostatin. Further studies revealed that H2S therapy increased the expression of the proliferation marker, Ki67, as well as increased the phosphorylation of endothelial NO synthase and the bioavailability of NO. Importantly, these changes were associated with an increase in vascular density within the H2S-treated hearts.
  
  
  CONCLUSIONS
  These results suggest that H2S therapy attenuates left ventricular remodeling and dysfunction in the setting of heart failure by creating a proangiogenic environment for the growth of new vessels.
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta, Georgia, 30308 and The Carlyle Fraser Heart Center.
authors.forename: David
authors.initials: D
authors.lastname: Polhemus
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan 466-8550.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Kondo
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta, Georgia, 30308 and The Carlyle Fraser Heart Center.
authors.forename: Shashi
authors.initials: S
authors.lastname: Bhushan
authors.affiliation: Departments of Pathology and Medicine, LSU Health Sciences Center-Shreveport, Shreveport, LA 7113.
authors.forename: Shyamal C
authors.initials: SC
authors.lastname: Bir
authors.affiliation: Departments of Pathology and Medicine, LSU Health Sciences Center-Shreveport, Shreveport, LA 7113.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Kevil
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan 466-8550.
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta, Georgia, 30308 and The Carlyle Fraser Heart Center.
authors.forename: David J
authors.initials: DJ
authors.lastname: Lefer
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta, Georgia, 30308 and The Carlyle Fraser Heart Center.
authors.forename: John W
authors.initials: JW
authors.lastname: Calvert
mesh_terms: D000498:Allyl Compounds / Q000378:metabolism / Q000494:pharmacology*; D043168:Angiostatins / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D005355:Fibrosis; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000494:pharmacology*; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D013440:Sulfides / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors; D014463:Ultrasonography; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D000498:Allyl Compounds; D019394:Ki-67 Antigen; D013440:Sulfides; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C042577:diallyl trisulfide; D009569:Nitric Oxide; D043168:Angiostatins; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D006862:Hydrogen Sulfide
keywords: H2S donor; angiogenesis; diallyl trisulfide; endothelial nitric oxide synthase; nitric oxide